Antibodies to Glutamic Acid Decarboxylase-65 is Associated with Total Daily Dose of Insulin Requirement in Children with Type 1 Diabetes
Abstract
BACKGROUND: Type 1 diabetes (T1D) mostly occurs due to the destruction of pancreatic beta cells due to autoimmune processes. Diagnosis of T1D can be established by examining the c-peptide levels and the markers of pancreatic autoantibodies, including glutamic acid decarboxylase 65 autoantibodies (GAD-65). However, the association between c-peptide and anti-GAD-65 toward patients’ clinical manifestations needs to be further explored. Hence, the aim of current study was to identify the association of anti-GAD65 with c-peptide and clinical characteristics in children with T1D.
METHODS: Case-control study involving 47 T1D children (T1D group) and 41 healthy children (control group) younger than 18 years old was conducted. Secondary data regarding subjects’ demographic characteristics and medical history were collected from subjects, and serum blood was drawn from each subject for the anti-GAD65 and c-peptide measurement. Anti-GAD65 and c-peptide levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) methods.
RESULTS: Anti-GAD65 antibody was detected in 78.7% T1D group, while only 2.43% were detected in control group subject (p=0.0000). The c-peptide level of T1D group was 0.07±0.19 nmol/L and control group was 1.5±0.77 nmol/L (p=0.0000). The total daily dose of insulin in subjects with positive anti-GAD65 was greater than in the negative anti-GAD65 (p=0.012). The sensitivity and specificity of the anti-GAD65 were 85.4% was 66.7%, respectively.
CONCLUSION: The results of this study show that anti-GAD65 was associated with total daily dose of insulin requirement in children with T1D.
KEYWORDS: diabetes mellitus, type 1 diabetes, anti-GAD65, c-peptide
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Libman I, Haynes A, Lyons S, Pradeep P, Rwagasor E, Tung JY, et al. ISPAD Clinical Practice Consensus Guideline 2022: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2022; 23(8): 1160-74, CrossRef.
International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussel: International Diabetes Federation; 2021, article.
Besser REJ, Bell KJ, Couper JJ, Ziegler AG, Wherrett DK, Knip M, et al. ISPAD Clinical Practice Consensus Guideline 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2022; 23(8): 1175-87, CrossRef.
Maraschin JF, Weinert LS, Murussi N, Witter V, Rodrigues TC, Rossato ER, et al. Influence of age at diagnosis and duration of diabetes on the positivity of glutamic acid decarboxylase antibody in South-Brazilian type 1 diabetes mellitus. Ann Clin Biochem. 2013; 50(3): 262-6, CrossRef.
Herawati E, Susanto A, Sihombing CN. Autoantibodies in diabetes mellitus. Mol Cell Biomed Sci. 2017; 1(2): 58-64, CrossRef.
Rochmah N, Faizi M, Hisbiyah Y, Farahdina F, Endaryanto A, Soetjipto. Predictive value of autoantibody markers in children with type 1 diabetes mellitus: A systematic review and meta-analysis. Turk Online J Qual Inq. 2022; 12(9): 4076-86, article.
Xie Z, Chang C, Zhou Z. Molecular mechanism in autoimmune type 1 diabetes: A critical review. Clin Rev Allergy Immunol. 2014; 47(2): 174-92, CrossRef.
Nieto J, Castillo B, Astudillo M, Tosur M, Balasubramanyam A, Pietropaolo M, et al. Islet autoantibody types mark differential clinical characteristics at diagnosis of pediatric type 1 diabetes. Pediatr Diabetes. 2021; 22(6): 882-8, CrossRef.
Vipin VP, Zaidi G, Watson K, Colman P, Prakash S, Agarwal S, et al. High prevalence of idiopathic (Islet-antibody negative) type 1 diabetes among Indian children and adolescents. Pediatr Diabetes. 2020; 22(1): 47-51, CrossRef.
Rochmah N, Faizi M, Windarti SW. Zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in children. Clin Exp Pediatr. 2020; 63(10): 402-5, CrossRef.
Heinonen MT, Moulder R, Lahesma R. New insights and biomarkers for type 1 diabetes: Review for Scandinavian Journal of Immunology. Scandinavian J Immunol. 2015; 82(3): 244-53, CrossRef.
Koo BK, Chae S, Kim CM, Kang MJ, Kim EG, Kwak SH, et al. Identification of novel autoantibodies in type 1 diabetes patients using a high-density protein microarray. Diabetes. 2014; 63(9): 3022-32, CrossRef.
Miersch S, Bian X, Wallstrom G, Sibani S, Logvinenko T, Wasserfall Ch, et al. Serological autoantibody profiling of type 1 diabetes by protein array. J proteomics. 2013; 94: 486-96, CrossRef.
El-Khateeb M, Mesri S, Juma M, El-Zaheri M, Ajlouni K. Antibodies to glutamic acid decarboxylase in Syrian and Jordanian type 1 diabetes patients and their siblings. Ann Saudi Med. 2003; 23(6): 376-80, CrossRef.
Leighton E, Sainsbury CAR, Jones GC. A practical review of c-peptide testing in diabetes. Diabetes Ther. 2017; 8(3): 475-87, CrossRef.
Jones AG, Hattersley AT. The clinical utility of c-peptide measurement in the care of patients with diabetes. Diabet Med. 2013; 30(7): 803-17, CrossRef.
Kawasaki E. Anti-islet autoantibodies in type 1 diabetes. Int J Mol Sci. 2023; 24(12): 10012, CrossRef.
Iqbal S, Jayyab AA, Alrashdi AM, Villarroya SR. The predictive ability of c-peptide in distinguishing type 1 diabetes from type 2 diabetes: A systematic review and meta-analysis. Endocr Pract. 2023; S1530: 5-8, CrossRef.
Minges KE, Whittemore R, Grey M. Overweight and obesity in youth with type 1 diabetes. Annu Rev Nurs Res. 2013; 31: 47-69, CrossRef.
Meiliana A, Wijaya A. Metaflammation, NLRP3 inflammasome, obesity and metabolic disease. Indones Biomed J. 2011; 3(3): 168-84, CrossRef.
Mottalib A, Kasetty M, Mar JY, Elseaidy T, Ashrafzadeh S, Hamdy O. Weight management in patients with type 1 diabetes and obesity. Curr Diab Rep. 2017; 17(10): 92, CrossRef.
Rahman MN, Diantini A, Fattah M, Barliana MI. Nutritional biomarkers for predicting pancreatic beta cell failure in central obesity. Indones Biomed J. 2021; 13(1): 19-26, CrossRef.
Kim KY, Kim MS, Lee YJ, Lee YA, Lee SY, Shin CH, et al. Glutamic acid decarboxylase and tyrosine phosphatase-related islet antigen-2 positivity among children and adolescents with diabetes in Korea. Diabetes Metab J. 2022; 46(6): 948-52, CrossRef.
Mahdi YR, Hashim U, Abdullah MA. Pancreatic autoantibodies in Sudanese children with newly diagnosed type 1 diabetes mellitus. Int J Diabetes Clin Res. 2019; 6(2):1-6, CrossRef.
Hagopian WA, Sanjeevi CB, Kockum I, Landin-Olsson M, Karlsen AE, Sundkrist G, et al. Glutamate decarboxylase, insulin, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children. J Clin Invest. 1995; 95(4): 1505-11, CrossRef.
Till AM, Kenk I, Rjasanowski I, Wassamuth R, Walschus U, Kerner W, et al. Autoantibody-defined risk for type 1 diabetes mellitus in a general population of schoolchildren: Results of the Karlsburg type 1 diabetes risk study after 18 years. Diabet Med. 2015; 32(8): 1008-16, CrossRef.
Sørgjerd EP, Thorsby PM, Torjesen PA, Skorpen F, Kvaløy K, Grill V. Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence; result from the HUNT study. BMJ Open Diab Res Care. 2015; 3(1): e000076, CrossRef.
Kuhtreiber WM, Washer SLL, Hsu E, Reinhold P, Burger D, Zheng H, et al. Low levels of c-peptide have clinical significance for established type 1 diabetes. Diabet Med. 2015; 32(10): 1346-53, CrossRef.
Majaliwa ES, Muze KC, Ndayongeje J, Mfinanga SG, Mmbaga BT, Ramaiya K. Correlation of c-peptide with complications observed in children and adolescents with type 1 diabetes in Tanzania: A cross-sectional survey. Glob Pediatr Health. 2023; 10: 3794-99, CrossRef.
Thunander M, Torn C, Petersson C, Ossianson B, Fornander J, Landin-Olsson M. Levels of c-peptide, body mass index and age, and their usefulness in classification of diabetes in relation to autoimmunity, in adults with newly diagnosed diabetes in Kronoberg, Sweden. Eur J Endocrinol. 2012; 166(6): 1021-29, CrossRef.
Shields BM, Peters JL, Cooper C, Lowe J, Knight BA, Powell RJ, et al. Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature. BMJ Open. 2015; 5(11): e009088, CrossRef.
DOI: https://doi.org/10.18585/inabj.v15i4.2377
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